Technical considerations for isolated limb perfusion: A consensus paper.

BACKGROUND: Isolated limb perfusion (ILP) is a well-established surgical procedure for the administration of high dose chemotherapy to a limb for the treatment of advanced extremity malignancy. Although the technique of ILP was first described over 60 years ago, ILP is utilised in relatively few specialist centres, co-located with tertiary or quaternary cancer centres. The combination of high dose cytotoxic chemotherapy and the cytokine tumour necrosis factor alpha (TNFα), mandates leakage monitoring to prevent potentially serious systemic toxicity. Since the procedure is performed at relatively few specialist centres, an ILP working group was formed with the aim of producing technical consensus guidelines for the procedure to streamline practice and to provide guidance for new centres commencing the technique. METHODS: Between October 2021 and October 2023 a series of face to face online and hybrid meetings were held in which a modified Delphi process was used to develop a unified consensus document. After each meeting the document was modified and recirculated and then rediscussed at subsequent meeting until a greater than 90% consensus was achieved in all recommendations. RESULTS: The completed consensus document comprised 23 topics in which greater than 90% consensus was achieved, with 83% of recommendations having 100% consensus across all members of the working group. The consensus recommendations covered all areas of the surgical procedure including pre-operative assessment, drug dosing and administration, perfusion parameters, hyperthermia, leakage monitoring and theatre logistics, practical surgical strategies and also post-operative care, response evaluation and staff training. CONCLUSION: We present the first joint expert-based consensus statement with respect to the technical aspects of ILP that can serve as a reference point for both existing and new centres in providing ILP.

Generation of Self-Induced Myocardial Ischemia in Large-Sized Cardiac Spheroids without Alteration of Environmental Conditions Recreates Fibrotic Remodeling and Tissue Stiffening Revealed by Constriction Assays.

A combination of human-induced pluripotent stem cells (hiPSCs) and 3D microtissue culture techniques allows the generation of models that recapitulate the cardiac microenvironment for preclinical research of new treatments. In particular, spheroids represent the simplest approach to culture cells in 3D and generate gradients of cellular access to the media, mimicking the effects of an ischemic event. However, previous models required incubation under low oxygen conditions or deprived nutrient media to recreate ischemia. Here, we describe the generation of large spheroids (i.e., larger than 500 µm diameter) that self-induce an ischemic core. Spheroids were generated by coculture of cardiomyocytes derived from hiPSCs (hiPSC-CMs) and primary human cardiac fibroblast (hCF). In the proper medium, cells formed aggregates that generated an ischemic core 2 days after seeding. Spheroids also showed spontaneous cellular reorganization after 10 days, with hiPSC-CMs located at the center and surrounded by hCFs. This led to an increase in microtissue stiffness, characterized by the implementation of a constriction assay. All in all, these phenomena are hints of the fibrotic tissue remodeling secondary to a cardiac ischemic event, thus demonstrating the suitability of these spheroids for the modeling of human cardiac ischemia and its potential application for new treatments and drug research.

Profilaxis primaria estándar versus prolongada de la infección por citomegalovirus en el trasplante de órgano sólido / Standard versus extended primary cytomegalovirus prophylaxis in solid organ transplantation

Antecedentes y objetivo:Se han comparado la eficacia y seguridad de la profilaxis primaria estándar o prolongada de la infección por citomegalovirus (CMV) en el trasplante de órgano sólido.Materiales y métodos:Estudio retrospectivo de los receptores CMV seronegativos de donante seropositivo (D+/R−) que recibieron profilaxis frente a CMV tras un trasplante de órgano sólido (2007-2017). Se comparó la frecuencia de infección por CMV en los 2 primeros años postrasplante en los receptores que recibieron profilaxis durante más o menos de 100 días. Se evaluó asimismo la mielotoxicidad durante la profilaxis.Resultados:Se analizaron 66 pacientes. De ellos el 43,9% (n=29) presentaron infección por CMV. El 68,2% (n=45) recibieron profilaxis prolongada, sin asociarse su uso con una menor tasa de infección (42,2 vs. 47,6%, p=0,44) ni de enfermedad posprofilaxis (15,6 vs. 19%, p=0,72). La profilaxis prolongada se asoció con una mayor frecuencia de mielotoxicidad (68,9 vs. 42,9%, p<0,05).Conclusiones:La prolongación de la profilaxis primaria más de 100 días no aumenta su efectividad pero sí la toxicidad hematológica. (AU)

Background and objective:We compared the efficacy and safety of standard vs. extended primary cytomegalovirus (CMV) prophylaxis in solid organ transplantation.Materials and methods:Retrospective cohort study of CMV seronegative recipients who received CMV prophylaxis after solid organ transplantation from seropositive donor (D+/R−) (2007–2017). CMV infection in the first two years after transplantation in recipients with prophylaxis longer or shorter than 100 days were compared.Results:CMV infection occurred in 29 of 66 patients (43.9%) with prophylaxis. Forty-five patients (68.2%) received extended prophylaxis. CMV infection and disease rates were not different between patients with extended and standard prophylaxis. However, extended prophylaxis was associated with a higher rate of myelotoxicity (68.9% vs. 42.9%, p<0.05).Conclusions:Extending primary CMV prophylaxis over 100 days did not prevent late-onset infection but it was associated with hematological toxicity. (AU)

Reexposición temprana a heparina durante el trasplante cardiaco de pacientes con trombocitopenia inducida por heparina y asistencia ventricular / Short-term heparin re-exposure during heart transplantation in patients with ventricular assist devices and acute heparin-induced thrombocytopenia

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I Informe del Registro Español de Tumores Postrasplante Cardiaco / First Report of the Spanish Post-Heart-Transplant Tumor Registry

Las neoplasias son una complicación frecuente y grave tras el trasplante cardiaco y una de las causas más importantes de muerte a largo plazo. El Registro Español de Tumores Postrasplante Cardiaco se inició en 2004, es online e incluye a todos los pacientes con trasplante cardiaco en España y con actualización continua de todos los tumores postrasplante. Los más frecuentes son cutáneos (54%), seguidos de los tumores no cutáneos no linfoides (39%) y linfomas (7%). La incidencia aumenta con la edad y el tiempo postrasplante y es mayor en varones. A los 15 años solo un 62% de los pacientes están libres de tumores. El pronóstico varía según el tipo de tumor. La incidencia de linfomas ha disminuido a la mitad en la última década. El Registro ayuda a conocer la incidencia, los factores de riesgo y el pronóstico de los tumores postrasplante y establecer estrategias de mejora (AU)

Neoplasia is a common and serious complication that occurs after heart transplantation and is one of the most important causes of death over the long term. The Spanish Post-Heart-Transplant Tumor Registry, which began in 2004, is an on-line record of all patients who have undergone heart transplantation in Spain. It includes continually updated information on post-transplantation tumors. The most common neoplasias are skin tumors (54%), followed by noncutaneous, nonlymphoid tumors (39%) and lymphomas (7%). Their incidence increases with age and time from transplantation and is higher in males. After 15 years, only 62% of patients are tumor-free. Prognosis varies according to the type of tumor. The incidence of lymphomas has decreased by half in the last decade. The Registry provides useful information on the incidence, risk factors and prognosis of tumors that occur after transplantation and can help in devising better management strategies (AU)

Comentario al artículo «Cierre percutáneo simultáneo de foramen oval permeable y orejuela izquierda» / Comment on the article "Simultaneous percutaneous closure of patent foramen ovale and left atrial appendage"

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Tratamiento percutáneo de la estenosis aórtica grave / Percutaneous treatment for severe aortic stenosis

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Registro Español de Trasplante Cardiaco. XXI Informe Oficial de la Sección de Insuficiencia Cardiaca y Trasplante Cardiaco de la Sociedad Española de Cardiología (1984-2009) / Spanish Heart Transplantation Registry. 21st Official Report of the Spanish Society of Cardiology Working Group on Heart Failure and Heart Transplantation (1984-2009)

Introducción y objetivos. El propósito de este artículo es presentar los resultados del trasplante cardiaco desde que se inició esta modalidad terapéutica en España en mayo de 1984. Métodos. Se ha realizado un análisis descriptivo de todos los trasplantes cardiacos realizados hasta el 31 de diciembre de 2009. Resultados. El número total de trasplantes fue de 6.048. El perfil clínico medio del paciente que se trasplantó en España en 2009 fue el de un varón de 53 años, diagnosticado de cardiopatía isquémica no revascularizable con depresión grave de la función ventricular y situación funcional avanzada, al que se implantó un corazón procedente de un donante fallecido por hemorragia cerebral, con una media de edad de 37 años y un tiempo en lista de espera de 106 días. El tiempo medio de supervivencia se ha incrementado con los años. Así, mientras en el total de la serie la probabilidad de supervivencia tras 1, 5, 10 y 15 años es del 78, el 67, el 53 y el 40% respectivamente, en los últimos 5 años la probabilidad de supervivencia tras 1 y 5 años es del 85 y el 73% respectivamente. La causa más frecuente de fallecimiento es el fallo agudo del injerto (17%), seguido de infección (16%), un combinado de enfermedad vascular del injerto y muerte súbita (14%), tumores (12%) y rechazo agudo (8%). Conclusiones. La supervivencia obtenida en España con el trasplante cardiaco, sobre todo en los últimos años, lo sitúa como el tratamiento de elección para cardiopatías irreversibles en situación funcional avanzada y sin otras opciones médicas o quirúrgicas establecidas (AU)

Introduction and objectives. The purpose of this report is to present the results obtained with heart transplantation in Spain from the first use of this therapeutic modality in May 1984. Methods. A descriptive analysis of all heart transplantations performed up to December 31, 2009 is presented. Results. In total, 6048 transplants were carried out. The typical clinical profile of a Spanish heart transplant patient in 2009 was that of a 53-year-old male who had been diagnosed with nonrevascularizable ischemic heart disease and who had severely impaired ventricular function and a poor functional status. The implanted heart typically came from a donor who had died from a brain hemorrhage (mean age 37 years) and the average time on the waiting list was 106 days. Mean survival time has increased progressively over the years. Whereas for the whole time series, the probability of survival at 1, 5, 10 and 15 years was 78%, 67%, 53% and 40%, respectively, for the past 5 years, the probability of survival at 1 and 5 years was 85% and 73%, respectively. The most frequent cause of death was acute graft failure (17%), followed by infection (16%), the combination of graft vascular disease and sudden death (14%), tumor (12%) and acute rejection (8%). Conclusions. The survival rates obtained in Spain with heart transplantation, especially in recent years, make the procedure the treatment of choice for patients who have irreversible heart failure and a poor functional status and for whom there are few other established medical or surgical options (AU)

Recomendaciones GESITRA-SEIMC y RESITRA sobre prevención y tratamiento de la infección por citomegalovirus en pacientes trasplantados / Consensus document from GESITRA-SEIMC on the prevention and treatment of cytomegalovirus in transplanted patients

La infección por citomegalovirus (CMV) es una complicación importante del trasplante. La última década se ha caracterizado por los avances en su tratamiento, reduciendo su morbilidad y la mortalidad. Estos avances han sido decisivos en el diagnóstico y prevención. Se han desarrollado técnicas de diagnóstico rápidas y sensibles. Entre las estrategias de prevención destaca el uso correcto de los productos sanguíneos, las inmunoglobulinas y los fármacos antivirales, empleados en profilaxis o en terapia anticipada. El reciente desarrollo de fármacos eficaces por vía oral como el valganciclovir permitirá el tratamiento ambulatorio de los pacientes infectados. Es necesario trasladar este conocimiento a la práctica clínica diaria. Con este objetivo el Grupo de Estudio de la Infección en el Trasplante (GESITRA) de la Sociedad Española de Microbiología Clínica y Enfermedades Infecciosas (SEIMC) ha desarrollado este documento de consenso que incluye las últimas recomendaciones en el tratamiento de la infección por CMV postrasplante (AU)

Cytomegalovirus (CMV) infection remains an important complication of transplantation. The last decade has been characterized by improvements to management that has reduced its morbidity and mortality. The advance has been particularly important in the diagnosis and prevention. Several techniques have been developed that allow the increasingly rapid and sensitive diagnosis. The different preventive strategies include use of appropriate blood products, immune globulin, and antiviral agents either as prophylaxis or pre-emptive therapy. The development of effective oral drugs as valganciclovir also represents a new advance. It is necessary to summarize these advances to facilitate the development of local policies reflecting recent changes. The Group of Study of Infections in Transplantation (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) has therefore produced actual recommendations in the management of CMV infection after transplantation (AU)